Diabetes Mellitus Overview

Diabetes Mellitus (DM)

• Disorder of carbohydrate metabolism
• High blood glucose levels
• Body's inability to produce or utilize insulin
• Increased morbidity and mortality
• Increased risk of cardiovascular disease (CVD), renal damage, peripheral vascular disease, neurological disorders, blindness, and amputation

Four Major Categories of Diabetes Mellitus

• Type 1 Diabetes Mellitus (T1DM): Lack of insulin production due to destruction of beta cells in pancreas
  • Insulin treatment required
• Type 2 Diabetes Mellitus (T2DM): 90% of those with diabetes
  • Insulin resistance present
• Gestational Diabetes Mellitus (GDM): Develops during pregnancy
  • Hormone changes reduce insulin sensitivity
  • Increased risk of macrosomia (large baby)
• Other: Pancreatitis, cystic fibrosis, and neonatal diabetes

Epidemiology

• Over 30 million people in the United States
• Prevalence parallels obesity increase
• Sedentary lifestyle contributes
• Prevalence increases with age
• Polygenic disorder, a mutation in multiple genes
• Environmental factors play a role

Etiology

• T1DM: Autoimmune destruction of beta cells
  • Antibodies present
  • Body does not produce insulin
• T2DM: More gradual onset
  • Insulin resistance
  • Insulin still produced
  • Sedentary behavior and obesity common factors

Insulin and Carbohydrate Ingestion

• Insulin is produced by beta cells and facilitates glucose movement from blood to cells
• Carbohydrate ingestion results in synchronous rise and fall of glucose and insulin
  • As glucose elevates, insulin increases

Insulin Facilitates Glucose Uptake

• Insulin increases glucose uptake by cells
• Helps regulate blood glucose levels

Carbohydrate Metabolism Overview

• Glucose: Used for energy, stored as glycogen, and converted to components of lipid molecules
• Glycogenesis: Glycogen formation, primarily in liver and muscle
• Glycogenolysis: Glycogen breakdown when blood glucose levels are low
• Gluconeogenesis: Amino acids and glycerol of lipids converted to glucose in the liver and kidneys

Ketone Formation and Diabetic Ketoacidosis (DKA)

• DKA primarily affects Type 1 diabetes
• Ketone formation occurs when glucose cannot be utilized
• Ketones are strong acids that alter blood pH, leading to metabolic acidosis

Blood Glucose Levels

• Normal Blood Glucose: 70-100 mg/dL (fasting)
• Hypoglycemia: Blood glucose below 70 mg/dL
• Impaired Glucose Tolerance (IGT): Prediabetes
  • Fasting blood glucose 100-125 mg/dL
• Diabetes: Fasting blood glucose greater than 126 mg/dL
• Postprandial Blood Glucose: Glucose after eating
  • Greater than 200 mg/dL indicates diabetes

Role of Insulin

• Muscle and Liver: Glycogenesis
  • Insulin is an anabolic hormone
• Adipose: Reduces lipolysis
• Hyperinsulinism: Increased insulin levels may occur to overcome insulin resistance
  • This may require increased insulin administration
• Hypoglycemia: Too much insulin can cause low blood glucose levels

Other Glucose-Regulating Hormones

• Glucagon: Released from alpha cells of pancreas when blood glucose levels are low
  • Injectable form used in severe hypoglycemia
• Somatostatin: Released from delta cells of pancreas
  • Diminishes the secretion of insulin and glucagon
  • Decreases gastrointestinal (GI) activity and slows absorption
• Incretins: Released from GI tissues
  • GLP-1 and GIP are GI glucose-regulating hormones that stimulate insulin and slow GI motility
• Cortisol: Released from the adrenal cortex
  • Increases blood glucose levels

Glucose-Regulating Signals From Pancreas

• The pancreas plays a critical role in blood glucose control
• Insulin and other hormones regulate glucose levels

T1DM: Pathological Mechanism

• Autoimmune disease caused by obesity and T cells attacking the body
• T cell mediated attack of beta cells
• Genetic influence
• DKA is often the presenting sign: Polyuria, polydipsia, and polyphagia

T2DM: Pathological Mechanism

• Insulin resistance with increased insulin levels
• Molecular-level mechanisms include oxidative stress, inflammation, insulin receptor mutation, and mitochondrial dysfunction
• Metabolic syndrome, characterized by hypertension, dyslipidemia, hyperinsulinism, and centralized obesity
• Hyperosmolar hyperglycemic syndrome (HHS) may occur but DKA is less common. Some insulin is still produced, preventing ketone formation

Gestational Diabetes Mellitus (GDM)

• Hormones of pregnancy increase insulin resistance
• Complications include fetal defects, premature delivery, newborn hypoglycemia, and macrosomia
• Screening involves a 2nd trimester oral glucose tolerance test (OGTT)
• GDM usually resolves after pregnancy but increases the risk of developing T2DM in the future

Diabetes Tests

• Blood Glucose: Fasting and random blood glucose levels
• Oral Glucose Tolerance Test (OGTT): 75g glucose ingested, blood glucose levels are measured
• Glycated Hemoglobin (A1c): Assesses blood glucose levels over the preceding 3 months
• Estimated Average Glucose (eAG): Average blood glucose over the last few months
• Islet Cell Autoantibodies (ICAs): Present in T1DM
• C-peptide Test: Indicator of endogenous insulin
  • C-peptide is released when the pancreas releases insulin
  • Helps differentiate between T1DM and T2DM

Diabetes Tests: Urinalysis

• Glucosuria: Elevated blood glucose leads to increased glucose filtration in the glomerulus
  • Glucose appears in urine when renal glucose transport maximum is exceeded
• Ketonuria: Ketone formation and renal filtration of ketones are elevated
  • More common in T1DM

Complications of DM

• Can be both acute and long-term
• Both hypoglycemia and hyperglycemia are possible
• Acute Complications: DKA (T1DM), HHS (T2DM)
• Long-Term Systemic Complications: Blindness, kidney failure, neuropathy, cardiovascular disease, and amputation

Hypoglycemia

• Blood glucose less than 70 mg/dL
• Causes: Excessive exogenous insulin, inadequate food intake, excessive physical activity, infections, illness, or drug interactions
• Compensatory response: Epinephrine, glucagon, and activation of the sympathetic nervous system (SNS) raise blood glucose levels
• Management: Fast-acting carbohydrates (15g), IV glucose, or subcutaneous injection of glucagon

Somogyi Effect and Dawn Phenomenon

• Somogyi Effect: Morning hyperglycemia due to hypoglycemia during sleep
  • Excessive insulin therapy or insulin peak may be contributing factors
  • Compensatory mechanisms raise blood glucose levels
• Dawn Phenomenon: Morning hyperglycemia without hypoglycemia during sleep
  • Nocturnal elevation in growth hormone may raise blood glucose levels
  • Cells utilize less glucose at night

Classic Signs of Diabetes Mellitus

• Polydipsia: Increased thirst due to high blood glucose increasing plasma osmolarity and fluid shifts
• Polyphagia: Increased appetite due to cells not being able to utilize glucose effectively
• Polyuria: Increased thirst and drinking (polydipsia) lead to increased renal glucose filtration and osmotic diuresis (water follows glucose into the urine)

Fluid Shifts

• High blood glucose disrupts fluid balance
• Fluid shifts from intracellular fluid (ICF) to extracellular fluid (ECF)

Fluid and Glucose in Urine

• Increased glucose and water in urine
• Reflects kidney function and fluid removal

Additional Signs of DM

• Blurred Vision: Accumulation of glucose in the aqueous fluid of the eye changes light refraction
• Fluid/Electrolyte Imbalance: Fluid shifts from ICF to ECF and electrolyte shifts
  • Can lead to dilutional hyponatremia and potassium shifting out of cells

Diabetic Ketoacidosis (DKA)

• Insulin lacking: Cells use glucose for fuel, preventing lipolysis
• Without Insulin: Ketone formation occurs as cells cannot utilize glucose
• Ketones: Strong acids that lead to metabolic acidosis
• DKA is more common in T1DM: Some insulin is still produced in T2DM, preventing ketone formation

Diabetic Ketoacidosis (DKA): Diagnostic Criteria and Presentation

• Diagnostic Criteria: Blood glucose greater than 250 mg/dL, pH less than 7.3, bicarbonate less than 18 mEq/dL, blood osmolarity greater than 20 mOsm/L
• Presentation: Nausea, vomiting, and dehydration

Hyperosmolar Hyperglycemic Syndrome (HHS)

• Hyperglycemia: Inability to facilitate glucose uptake
  • Gluconeogenesis and glycogenolysis exacerbate hyperglycemia
• Hyperosmolarity: Elevated blood glucose leads to osmotic diuresis and polyuria
• Clinical Progression: Gradual development over days to weeks
• Patient Presentation: Weakness, poor tissue turgor, tachycardia, thready pulse, and confusion (25% of patients present in coma)
• Causes: Infection, trauma, and noncompliance with diabetes management
• Treatment: Fluids are administered first, followed by insulin to address plasma osmolarity issues

Long-Term Complications of DM

• Arteriosclerosis: Damage to endothelial cells
  • Leads to foam cells upon macrophages
• Peripheral Angiopathy: Lack of circulation
• Diabetic Retinopathy: Damaged eye vessels
• Diabetic Neuropathy: Damaged kidneys
  • Nephrocytes are damaged
• Autonomic Neuropathy:
• Diabetic Nephropathy:
• Poor Wound Healing: Decreased blood flow and high sugar levels create an environment where bacteria can grow easily, leading to slow healing
• Immunosuppression:

Long-Term Complications of DM: Factors and Effects

• Arteriosclerosis: Myocardial infarction (heart attack)
• Peripheral Angiopathy: Limb ischemia (lack of oxygen to blood vessels)
• Diabetic Retinopathy: Blindness
• Diabetic Neuropathy: Lack of sensation in lower extremities, burning, tingling
• Autonomic Neuropathy: Poor autonomic control
• Diabetic Nephropathy: Kidney failure
• Poor Wound Healing: Gangrene (necrotic tissue)

Long-Term Complications of DM: Risk Factors

• Duration of Chronic Hyperglycemia: - Damage to small and large arterial vessels - End-organ damage - Poor wound healing - Macrovascular damage
• Genetic Susceptibility:

DM and Atherosclerosis

• Acute Cardiac Events: 2-4 times more likely in diabetes patients
• Atherosclerosis: Affects large and small arteries
• Vascular Damage: Multiple processes contribute to damage, all linked to hyperglycemia and oxidative stress

DM and Peripheral Neuropathy

• Distal, Symmetric Polyneuropathy: Neural arteries are damaged, starting in the feet and progressing upwards
• Sensorimotor Nerves: Burning and tingling in the feet, blunted pain sensation
• Signs of Injury: Silent heart attack, motor weakness, gait abnormality, Charcot joint

DM and Autonomic Neuropathy

• Cardiac: Tachycardia, hypotension
• GI: Gastroparesis, gastric emptying abnormality, anorexia, nausea, bowel dysfunction
• Urinary: Increased risk of urinary tract infections (UTIs)
• Reproductive: Erectile dysfunction
• Temperature Regulation: Decreased sweating, hyperthermia, dry skin
• Glycemic Control: Hypoglycemia may be less noticeable due to altered signs and symptoms

DM and Susceptibility to Infection

• WBC Function: Reduced white blood cell function
• Increased Colonization: Staph aureus and Candida (yeast)
  • High glucose levels change vaginal pH allowing Candida to proliferate

DM and Amputation

• Diabetic Foot Complications: Most common cause of nontraumatic lower extremity amputation
  • Peripheral neuropathy, poor circulation, and suppressed immune response lead to increased infection susceptibility
  • Can lead to gangrene and amputation
  • Osteomyelitis (bone infection)

DM and Poor Wound Healing

• Reduced circulation and high sugar levels create environments that make it difficult for wounds to heal

DM and Foot Care

• Examine feet for sensation, including light touch
• Assess Achilles tendon reflex
• Check toe position
• Examine for injuries or wounds

DM and Retinopathy/Blindness

• Leading cause of blindness in adults
• Retinal Circulatory Damage: Microaneurysms, macular edema, and cotton wool spots (infarcted regions of retina)
• Proliferative Retinopathy: New vessel growth that is fragile and may rupture, leading to retinal detachment
• Regular Fundoscopic and Ophthalmological Exams: Critical to detect and manage retinopathy

DM and Nephropathy

• Renal Failure: Damage to the glomerular capillaries
  • Microalbuminuria (protein in the urine) may be present
• Glomerular Basement Membrane: Thickens due to glycosylation end-products
• Activation of RAAS: Worsens the problem by elevating blood pressure

DM and Dermatological Issues

• Prolonged Wound Healing and Ulcer Formations:
• Diabetic Skin Spots: Hyperpigmented areas
• Acanthosis Nigricans: Tiny, hyperpigmented, macular lesions
• Lipoatrophy: May occur at insulin injection sites

DM and Psychological Resistance

• Depression: Twice as common in individuals with diabetes
  • Guilt, discouragement, and self-blame are common, especially with type 2 diabetes
  • Anxiety related to disease management
  • Denial and noncompliance may occur
• Psychological Insulin Resistance: Refusal to comply with insulin management

DM and Eating Disorders

• Young Women with T1DM: At higher risk for eating disorders
• Insulin Purging: Restricting or skipping insulin usage to stimulate lipolysis and weight loss
• Suspect Eating Disorder: Patients with recurrent DKA or chronically poor glycemic control

DM Treatment Overview

• Blood Glucose Control: Managing both hyperglycemia and hypoglycemia
• Glycemic Control: Primary goal to reduce the risk of complications
• Reduce CVD Risk: Lipid panels, LDL below 60 mg/dL, and triglyceride management